How does one mark a book with more than one genre hierarchy? For example, if I have a book in Nonfiction.Memoir but would also like to add the genre Humor, how would I do that?

Since I can't find Genre as a column or field in calibre the question isn't simple. In your example above I would have the tags Nonfiction, Memoir and Humor associated with the book and use the search feature to find sub groups.

I assume you are trying to follow this section of calibre's user manual. Personally I haven't seen a reason to create any genre hierarchy since, for my needs, being able to search on multiple tags (including or excluding tags as needed) is simple using calibre's tag browser.

Hopefully either the manual I linked to will help you or someone will stop by who can guide you in this feature's use.